Biology subjects

zhao, c.

Publications and source records attributed to zhao, c..

7 recordsLinked to original sources

bioRxiv2026

A cis-regulatory variant in ASIP causes gray coat color in the donkey

BackgroundGray is one of the relatively rare coat colors in donkeys. The Hetian Gray donkey is a distinctive indigenous breed from the Xinjiang Uygur Autonomous Region of Northwestern China, characterized by progressive hair depigmentation with aging while retaining dark skin pigmentation. However, the genetic basis underlying this unique gray coat color phenotype remains unclear. ResultsTo elucidate the genetic basis, we conducted whole-genome resequencing of Gray and non-Gray donkeys. Genome-wide selection signature analyses identified a candidate region on chromosome 15. Subsequent fine-mapping using mass spectrometry-based genotyping of 42 loci refined the candidate interval and revealed a SNP within intron 2 of the ASIP gene, located in a genomic fragment with highly similar sequences, showing complete association with the gray coat color. Association analysis in an expanded population further confirmed a strong correlation between this variant and the gray phenotype. Gene expression analyses also supported the role of ASIP in regulating pigmentation in donkeys. ConclusionsThese findings identify a genetic determinant of gray coat color in donkeys and provide new insights into the molecular mechanisms underlying age-related depigmentation in domestic animals.

genomics↗

bioRxiv2026

Heterotrimeric G protein αi2 Sequesters RasGAP to Control Neutrophil Sensitivity and Chemotaxis

G protein-coupled receptors (GPCRs) direct neutrophil chemotaxis through heterotrimeric G proteins, yet the downstream effectors of the predominant Gai isoform, Gai2, remain incompletely defined. Here we identify the Ras GTPase-activating protein CAPRI (RASA4) as a functional effector of Gai2 that links GPCR signaling to Ras adaptation. Using AlphaFold3-based structural modeling and binding free-energy calculations and experimental verification, we reveal that constitutively active and structurally altered Gai2 mutants (Q205L and T182A) exhibit enhanced binding to CAPRI. Neutrophils expressing these mutants display elevated basal Ras activity, heightened sensitivity to chemoattractant, and improved chemotaxis in low- or subsensitive-concentration gradients. However, these cells exhibit excessive Ras activation and impaired chemotaxis at high, saturating chemoattractant concentrations, while maintaining near-normal responses at intermediate concentrations. These results reveal an upward shift in the concentration range for efficient chemotaxis. Our findings not only establish a previously unrecognized Gai2-CAPRI signaling axis that tunes Ras adaptation but also define a mechanism by which heterotrimeric G proteins calibrate leukocyte navigation across diverse chemoattractant gradients.

immunology↗

bioRxiv2026

A Phospho-Switch for Cell Fate Control

Cell fate control is thought to be complex, likely involving both cell intrinsic and extrinsic factors, and remains ill-defined at the molecular level. Here we show a phospho-switch controls cell fate both in vitro and in vivo. We first show that SALL4 is phosphorylated at multiple sites, but only T903 as the primary one as SALL4T903A lost BAF interaction and [~]90% activity in reprogramming. Mechanistically, we demonstrate that SALL4pT903 is sensitive to BMP4 signaling through DUSP9 axis. Finally, we show by tetraploid embryo complementation that mESCs harboring SALL4T903A can sustain embryo development but with severe defects including cranial hypoplasia and flattened skull vault after birth. A genome wide search identifies 608 transcription factors harboring the same HTG motif sandwiched by two zinc fingers, suggesting that this phospho-switch may be a conserved mechanism to control cell fate. In briefA phosphorylation switch, pT903, in SALL4 governs cell fate by modulating BAF complex interaction in response to BMP4-DUSP9 signaling, as its dephosphorylation abrogates reprogramming and causes cranial defects in mice, suggesting that such switches may broadly regulate cell fate machinery. HighlightsO_LIA T903 phospho-switch in SALL4 gates BAF interaction to orchestrate gene activation and reprogramming C_LIO_LIBMP4-DUSP9 signaling converges on SALL4pT903 dephosphorylation to couple extracellular cues with cell fate determination C_LIO_LIDisrupting the SALL4-T903 phospho-switch causes severe postnatal developmental defects in mice. C_LIO_LIThe HTGE motif may function as a central switch on key transcription factors for sensing upstream signals C_LI

developmental biology↗

bioRxiv2025

Telomere-to-telomere gap-free genome assembly of a male donkey and the identification of novel SVs associated with functional genes

Previous assemblies of the donkey genome remain with gaps and structural errors, and a complete donkey genome will greatly facilitate genetic research related to donkeys. In the present study, a 2.78-Gb telomere-to-telomere gap-free donkey genome (CAU_T2T_donkey) was assembled, including a 29.78-Mb Y chromosome, aided by ONT and trio-binning approach. CAU_T2T_donkey corrected the structural errors of previous assemblies and added a total of 153.8-Mb previously unresolved regions and 354 genes to the reference genome EquAss-T2T_v2. We identified a 1.9-Mb PAR on CAU_T2T_donkey-chromosome Y, and added 17.1Mb regions and 75 new genes to the chromosome Y of the previous reference genome ASM1607732v2. Multi-copy genes, such as TSPY, L1RE, ETY, HSFY, and ETSTY were also identified in CAU_T2T_donkey-chromosome Y. Totally 6 types of repetitive sequences in centromeric regions were identified, and the features of the centromeric regions were revealed, and satellite-free centromeres were identified. We aligned HiFi long-read sequences of donkeys from six breeds against CAU_T2T_donkey and identified SVs in previously unresolved regions, and some of the novel SVs were located in functional genes, such as AOX1 (Chr4:DEL61), ASIC2 (Chr13:INS954), and Twist2 (Chr19:DEL98).

genomics↗

bioRxiv2025

From Development to Regeneration: Insights into Flight Muscle Adaptations from Bat Muscle Cell Lines

Skeletal muscle regeneration depends on muscle stem cells, which give rise to myoblasts that drive muscle growth, repair, and maintenance. In bats--the only mammals capable of powered flight--these processes must also sustain contractile performance under extreme mechanical and metabolic stress. However, the cellular and molecular mechanisms underlying bat muscle physiology remain largely unknown. To enable mechanistic investigation of these traits (Graphical Abstract), we established the first myoblast cell lines from the pectoralis muscle of Pteronotus mesoamericanus, a highly maneuverable aerial insectivore. Using both spontaneous immortalization and exogenous hTERT/CDK4 overexpression, we generated two stable cell lines that retain proliferative capacity and differentiate into contractile myotubes. These cells exhibit frequent spontaneous contractions, suggesting robust functional integrity at the neuromuscular junction. In parallel, we performed transcriptomic and metabolic profiling of native pectoralis tissue to define molecular programs supporting muscle specialization. Gene expression analyses revealed enriched pathways for muscle metabolism, development, and regeneration, highlighting the supporting roles in tissue maintenance and repair. Consistent with this profile, the flight muscle is triglyceride-rich, which serves as an important fuel source for energetically demanding processes, including muscle contraction and cellular recovery. Integration of transcriptomic and metabolic data identified three key metabolic modules--glucose utilization, lipid handling, and nutrient signaling--that likely coordinate ATP production and support metabolic flexibility. Together, these complementary tools and datasets provide the first in vitro platform for investigating bat muscle research, enabling direct exploration of muscle regeneration, metabolic resilience, and evolutionary physiology. Graphical AbstractEstablishment of bat muscle cell cultures from the Mesoamerican mustached bat (P. mesoamericnus) provides an in vitro platform to investigate muscle regeneration and flight muscle biology. The pectoralis major muscle was isolated to generate primary myoblast cultures, which were expanded and immortalized using hTERT/CDK4. The resulting myoblast lines retain proliferative and differentiation capacity. RNA sequencing of native pectoralis muscle tissue revealed molecular signatures of myogenic regulation, stress resilience, and tissue remodeling, supporting the relevance of these in vitro models for studying muscle maintenance and regenerative mechanisms. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/662643v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@490f49org.highwire.dtl.DTLVardef@8ab615org.highwire.dtl.DTLVardef@b840e1org.highwire.dtl.DTLVardef@ab92eb_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Modelling cell type-specific lncRNA regulatory network in autism with Cycle

Autism spectrum disorder (ASD) is a class of complex neurodevelopment disorders with high genetic heterogeneity. Long non-coding RNAs (lncRNAs) are vital regulators that perform specific functions within diverse cell types and play pivotal roles in neurological diseases including ASD. Therefore, studying the specific regulation of lncRNAs in various cell types is crucial for deciphering ASD molecular mechanisms. Existing computational methods utilize bulk transcriptomics data across all of cells or samples, which could reveal the commonalities of lncRNA regulation in the pathogenesis of ASD, but ignore the specificity of lncRNA regulation across various cell types. Here, we present Cycle (Cell type-specific lncRNA regulatory network) to construct the landscape of cell type-specific lncRNA regulation in ASD. We have found that each ASD cell type is unique in lncRNA regulation, and more than one-third and all of cell type-specific lncRNA regulatory networks are characterized as scale-free and small-world, respectively. Across 17 ASD cell types, we have discovered 19 rewired and 11 conserved modules, and eight rewired and three conserved hubs underlying within the discovered cell type-specific lncRNA regulatory networks. Moreover, the discovered rewired and conserved modules and hubs are significantly enriched in ASD-related terms. Furthermore, more similar ASD cell types tend to be connected with higher strength in the constructed cell similarity network. Finally, the comparison results demonstrate that Cycle is a potential method for uncovering cell type-specific lncRNA regulation.

bioinformatics↗

bioRxiv2020

One-Step Rapid Quantification of SARS-CoV-2 Virus Particles via Low-Cost Nanoplasmonic Sensors in Generic Microplate Reader and Point-of-Care Device

The spread of SARS-CoV-2 virus in the ongoing global pandemics has led to infections of millions of people and losses of many lives. The rapid, accurate and convenient SARS-CoV-2 virus detection is crucial for controlling and stopping the pandemics. Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swab or saliva samples. Here we developed a method for rapid and direct optical measurement of SARS-CoV-2 virus particles in one step nearly without any sample preparation using a spike protein specific nanoplasmonic resonance sensor. We demonstrate that we can detect as few as 30 virus particles in one step within 15 minutes and can quantify the virus concentration linearly in the range of 103 vp/ml to 106 vp/ml. Measurements shown on both generic microplate reader and a handheld smartphone connected device suggest that our low-cost and rapid detection method may be adopted quickly under both regular clinical environment and resource-limited settings.

bioengineering↗